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The Influence of Therapeutic Radiation on the Patterns of Bone Remodeling in Ovary-Intact and Ovariectomized Mice

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Abstract

Our purpose was to characterize changes in bone remodeling associated with localized radiation that models therapeutic cancer treatment in ovary-intact (I) and ovariectomized (OVX) mice and to evaluate the influence of radiation on the pattern of bone mineral remodeling. Young adult, female BALB/c mice, I and OVX, were used (n = 71). All mice were intravenously injected with 15 μCi 45Ca. Thirty days post-45Ca administration, the hind limbs of 17 mice were exposed to a single dose of 16 Gy radiation (R). The time course of 45Ca excretion, serum CTx and osteocalcin markers, and cancellous bone volume fraction (BV/TV) and cortical thickness (Ct.Th) of the distal femur were assayed. Cellular activity and dynamic histomorphometry were performed. Irradiation resulted in rapid increases in fecal 45Ca excretion compared to control groups, indicating increased bone remodeling. CTx increased rapidly after irradiation, followed by an increase in osteocalcin concentration. BV/TV decreased in the I mice following irradiation. Ct.Th increased in the OVX groups following irradiation. I+R mice exhibited diminished osteoblast surface, osteoclast number, and mineral apposition. Our murine model showed the systemic effects (via 45Ca excretion) and local effects (via bone microarchitecture and surface activity) of clinically relevant, therapeutic radiation exposure. The I and OVX murine models have similar 45Ca excretion but different bone microarchitectural responses. The 45Ca assay effectively indicates the onset and rate of systemic bone mineral remodeling, providing real-time assessment of changes in bone histomorphometric parameters. Monitoring bone health via a bone mineral marker may help to identify the appropriate time for clinical intervention to preserve skeletal integrity.

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Acknowledgments

This work was supported by the National Institutes of Health (grants 1R03AR055333-01A1 and 1K12-HD055887-01) and by the PHS Cancer Center Support (grant P30 CA77398) and the Joseph E. Wargo cancer research fund from the University of Minnesota. S. K. H. is a scholar of the Building Interdisciplinary Careers in Women’s Health program. The authors acknowledge and thank the University of Minnesota – University Imaging Center, for aid in UV microscopy and Luke Arentsen, Kathleen Coghill, and Eftu Boru for laboratory assistance as well as Rajaram Gopalakrishnan, Kim Mansky, and Seymor Levitt for fruitful discussion pertaining to this experiment and report.

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The authors also state that they have full control of all primary data and they agree to allow Calcified Tissue to review their data if requested.

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Authors and Affiliations

  1. Department of Therapeutic Radiology, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 494, Minneapolis, MN, 55455, USA

    Susanta K. Hui, Gregory R. Fairchild, Louis S. Kidder & Manju Sharma

  2. Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Susanta K. Hui & Douglas Yee

  3. United States Navy, Medical Service Corps, Minneapolis, MN, USA

    Gregory R. Fairchild

  4. Departments of Medicine and Orthopaedic Surgery, Medical College of Georgia, Augusta, GA, USA

    Maryka Bhattacharya

  5. Biostatistics and Informatics Shared Resource of Masonic Cancer Center, Minneapolis, MN, USA

    Scott Jackson

  6. Department of Biostatistics, University of Minnesota, Minneapolis, MN, USA

    Chap Le

  7. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    Anna Petryk

  8. Department of Genetics Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA

    Anna Petryk

  9. Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, MN, USA

    Mohammad Saiful Islam

  10. Department of Medicine Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Douglas Yee

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  1. Susanta K. Hui
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Correspondence to Susanta K. Hui.

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Hui, S.K., Fairchild, G.R., Kidder, L.S. et al. The Influence of Therapeutic Radiation on the Patterns of Bone Remodeling in Ovary-Intact and Ovariectomized Mice. Calcif Tissue Int 92, 372–384 (2013). https://doi.org/10.1007/s00223-012-9688-0

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  • DOI: https://doi.org/10.1007/s00223-012-9688-0

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